Despite recent implementation of peripartum chemoprophylaxis of carriers, Group B Streptococci (GBS) remain the leading cause of neonatal sepsis in the U.S. In addition, pregnancy-related morbidity occurs in nearly 50,000 women annually, and GBS disease among adults with immunocompromising chronic illness was recently recognized as an important cause of morbidity and mortality. Widespread use of a successful multivalent GBS conjugate vaccine could significantly alleviate the mortality and morbidity associated with this pathogen. The ultimate public health goal is the licensure of an efficacious vaccine to prevent GBS infection in those at risk, including newborn infants, postpartum women, and immunocompromised adults. Excellent progress has been made in developing vaccines against GBS disease and in understanding the epidemiology and basic biology of the organism, and the work under this renewal contract will build on this progress. While infections due to GBS have been increasing over the last thirty years, there has also been a resurgence of invasive Group A streptococcal (GAS) disease that began in the 1980s and has continued unabated. The reasons for the resurgence remain poorly understood and mandate investigations into basic pathogenic mechanisms of GAS disease in order to understand the recent changes in patterns and severity of infections and to design appropriate intervention strategies. Based on the trends in streptococcal disease, four areas have been identified as topics having the highest priority for investigation in the contract renewal period: (1) study of pathogenic mechanisms of streptococcal infections (GBS and GAS); (2) epidemiologic surveillance (GBS); (3) production and human testing of vaccines (GBS); and (4) laboratory support for vaccine trials (GBS).